Targeted opioid that hones in on inflamed tissues stops colitis pain without side effects

A targeted opioid that only treats diseased tissues and spares healthy tissues relieves pain from inflammatory bowel disease without causing side effects, according to new research published in the journal Gut.
The study, led by researchers at New York University College of Dentistry and Queen’s University in Ontario, was conducted in mice with colitis, an inflammatory bowel disease marked by inflammation of the large intestine.
Opioids, which are used to treat chronic pain in people with inflammatory bowel disease, relieve pain by targeting opioid receptors, including the mu opioid receptor. When opioids activate the mu opioid receptor in healthy tissues, however, they can cause severe and life-threatening side effects, including difficulty breathing, constipation, sedation, and addiction.
“We wanted to understand whether it is possible to activate this receptor only in diseased tissues and not in normal tissues,” said senior study author Nigel Bunnett, PhD, professor and chair of the Department of Molecular Pathobiology at NYU College of Dentistry. “Essentially, can you control pain without triggering these devastating side effects?”
The answer may lie in a novel opioid called NFEPP, discovered by Christoph Stein, MD, of Charité-Universitätsmedizin Berlin, a collaborator on the Gut study. NFEPP is a reengineered form of the opioid fentanyl; an added fluorine atom helps the drug to only bind to the mu opioid receptor in an acidic environment. This steers NFEPP to diseased tissues — sites of inflammation or injury — which become acidic due to changes in the tissues’ metabolism.
The researchers investigated the use of NFEPP and fentanyl in mice with colitis, which caused their gut tissue to be mildly acidic. Both NFEPP and fentanyl inhibited colon pain in mice with colitis. However, in sharp contrast to fentanyl, NFEPP did not cause side effects such as constipation, suppressed breathing, and altered movement. In healthy mice without inflammatory bowel disease, NFEPP did not alter pain activity or cause side effects.
“The preference of NFEPP for activating opioid receptors in acidic tissues accounts for its ability to selectivity relieve pain in the inflamed but not healthy colon,” said Bunnett. “By sparing healthy tissues, we avoided the detrimental side effects seen with fentanyl use.”
The researchers are now collecting tissue samples from people with inflammatory bowel disease to determine whether their colons, like those in mice, are also acidic environments. If so, they plan to test NFEPP’s ability to inhibit pain in the human gut and ultimately conduct clinical trials.
“Treatments designed to preferentially engage opioid receptors in diseased tissues could offer the potential for effective pain relief without the side effects. These drugs would represent a major advance in the treatment of painful diseases, including inflammatory bowel disease and cancer,” said Bunnett. “More broadly, engineering drugs beyond pain treatments that target only diseased tissues could open the door to more effective and precise therapies for a wide range of disorders.”
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Study ratifies link of processed meat to cardiovascular disease and early death

A global study led by Hamilton scientists has found a link between eating processed meat and a higher risk of cardiovascular disease. The same study did not find the same link with unprocessed red meat or poultry.
The information comes from the diets and health outcomes of 134,297 people from 21 countries spanning five continents, who were tracked by researchers for data on meat consumption and cardiovascular illnesses.
After following the participants for almost a decade, the researchers found consumption of 150 grams or more of processed meat a week was associated with a 46 per cent higher risk of cardiovascular disease and a 51 per cent higher risk of death than those who ate no processed meat.
However, the researchers also found moderate levels of consumption of non-processed meats had a neutral effect on health.
“Evidence of an association between meat intake and cardiovascular disease is inconsistent. We therefore wanted to better understand the associations between intakes of unprocessed red meat, poultry, and processed meat with major cardiovascular disease events and mortality,” said Romaina Iqbal, first author of the study and an associate professor at the Aga Khan University in Karachi, Pakistan.
“The totality of the available data indicates that consuming a modest amount of unprocessed meat as part of a healthy dietary pattern is unlikely to be harmful,” said Mahshid Dehghan, investigator for the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences.
The Prospective Urban Rural Epidemiology (PURE) study was launched in 2003 and is the first multinational study that provides information on the association between unprocessed and processed meat intakes with health outcomes from low, middle and high-income countries.
“The PURE study examines substantially more diverse populations and broad patterns of diet, enabling us to provide new evidence that distinguishes between the effects of processed and unprocessed meats,” said senior author Salim Yusuf, executive director of the PHRI.
Participants’ dietary habits were recorded using food frequency questionnaires, while data was also collected on their mortality and major cardiovascular disease events. This allowed researchers to determine the associations between meat consumption patterns and cardiovascular disease events and mortality.
The authors believe that additional research may improve current understanding of the relationship between meat consumption and health outcomes. For example, it is unclear what study participants with lower meat intakes were eating instead of meat, and if the quality of those foods differed between countries.
Non-meat food substitutes may have implications in further interpreting the associations between meat consumption and health outcomes. Nonetheless, the study’s authors believe their findings “indicate that limiting the intake of processed meat should be encouraged.”
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Exercise, healthy diet in midlife may prevent serious health conditions in senior years

Following a routine of regular physical activity combined with a diet including fruits, vegetables and other healthy foods may be key to middle-aged adults achieving optimal cardiometabolic health later in life, according to new research using data from the Framingham Heart Study published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.
Cardiometabolic health risk factors include the metabolic syndrome, a cluster of disorders such as excess fat around the waist, insulin resistance and high blood pressure. Presence of the metabolic syndrome may increase the risk of developing heart disease, stroke and Type 2 diabetes.
Researchers noted it has been unclear whether adherence to both the U.S. Department of Health and Human Services’ 2018 Physical Activity Guidelines for Americans and their 2015-2020 Dietary Guidelines for Americans — as opposed to only one of the two — in midlife confers the most favorable cardiometabolic health outcomes later in life. The physical activity guidelines recommend that adults achieve at least 150 minutes of moderate or 75 minutes of vigorous physical activity per week, such as walking or swimming. The dietary guidelines, which were updated in January 2021, offer suggestions for healthy eating patterns, nutritional targets and dietary limits.
In an analysis of data from participants of the Framingham Heart Study, which began more than 70 years ago in Framingham, Massachusetts, investigators examined data from 2,379 adults ages 18 and older and their adherence to the two guidelines. They observed that meeting a combination of the two recommendations during midlife was associated with lower odds of metabolic syndrome and developing serious health conditions as participants aged in their senior years in 2016-2019 examinations.
“Health care professionals could use these findings to further promote and emphasize to their patients the benefits of a healthy diet and a regular exercise schedule to avoid the development of numerous chronic health conditions in the present and in later life,” said corresponding author Vanessa Xanthakis, Ph.D., FAHA, assistant professor of medicine and biostatistics in the Section of Preventive Medicine and Epidemiology at Boston University School of Medicine in Boston. “The earlier people make these lifestyle changes, the more likely they will be to lower their risk of cardiovascular-associated diseases later in life.”
Study participants were selected from the third generation of the Framingham Heart Study. Participants (average age 47, 54% women) were examined between 2008 and 2011. Researchers evaluated physical activity using a specialized device known as an omnidirectional accelerometer. The device, which tracks sedentary and physical activity, was worn on the participant’s hip for eight days. Researchers also collected dietary information from food frequency questionnaires to measure the kinds and levels of food and nutrients consumed.
In this investigation, researchers observed that among all participants, 28% met recommendations of both the physical activity and dietary guidelines, while 47% achieved the recommendations in only one of the guidelines. Researchers also observed that: participants who followed the physical activity recommendations alone had 51% lower odds of metabolic syndrome; participants who adhered to the dietary guidelines alone had 33% lower odds; and participants who followed both guidelines had 65% lower odds of developing metabolic syndrome.”It is noteworthy that we observed a dose-response association of adherence to diet and physical activity guidelines with risk of cardiometabolic disease later in life,” Xanthakis said. “Participants who met the physical activity guidelines had progressively lower risk of cardiometabolic disease as they increased adherence to the dietary guidelines.”
All study participants were white adults, therefore, the findings cannot be generalized to people in other racial or ethnic groups. Additional studies with a multiethnic participant sample are needed, researchers said.
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Turning back the clock on a severe vision disorder

Gustavo Aguirre and William Beltran, veterinary ophthalmologists and vision scientists at the University of Pennsylvania School of Veterinary Medicine, have studied a wide range of different retinal blinding disorders. But the one caused by mutations in the NPHP5 gene, leading to a form of Leber congenital amaurosis (LCA), is one of the most severe.
“Children with this disorder are not visual,” says Aguirre. “They have a wandering, searching look on their faces and are usually diagnosed at a young age.”
A nearly identical disease naturally occurs in dogs. In a new paper in the journal Molecular Therapy, Aguirre, Beltran, and colleagues at Penn and other institutions have demonstrated that a canine gene therapy can restore both normal structure and function to the retina’s cone photoreceptor cells, which, in LCA patients, otherwise fail to develop normally. Delivering a normal copy of either the canine or human version of the NPHP5 gene restored vision in treated dogs.
“What’s amazing is that you can take this disease in which cone cells have incompletely formed, and the therapy restores their function — they had no function whatsoever before — and recover their structure,” says Aguirre.
“That plasticity is incredible and gives us a lot of hope,” Beltran says.
LCA includes a wide range of inherited vision disorders characterized by blindness that strike in early childhood. The form of LCA associated with NPHP5 mutations is rare, affecting about 5,000 people worldwide. Known as a ciliopathy, it affects the cilia of cells of the retina. The cilia cells are antennalike structures on photoreceptor cells that translate the energy from light into visual signals.

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Experimental treatment offers hope of fertility for early menopausal women

Menopause typically signals the end of a woman’s ability to become pregnant. However, in a small new study, a novel approach of administering platelet-rich plasma and gonadotropins near the ovarian follicles is showing promise in restoring ovarian function. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).
As more women look to build their careers before pursuing motherhood, the average age of conceiving a child continues to be pushed back. For some of these women, however, their hope of becoming pregnant is cut short by the onset of early menopause, which is described as the cessation of ovarian function at or before the age of 45 years. It is estimated that roughly 12.2% of women experience early menopause. For these women, the only chance of becoming pregnant is with donor eggs.
Multiple treatment options have previously been investigated, including standard, controlled ovarian stimulation. Platelet-rich plasma has been used in women with primary ovarian insufficiency, but few pregnancies and live births resulted. With the failure of these somewhat traditional treatments, more novel approaches, such as methods for inducing the growth of ovarian follicles, are being pursued.
In this new, small-scale pilot study, platelet-rich plasma and gonadotropins were injected into the ovaries of study participants, with some fairly amazing results. After treatment, 11 of the 12 study participants resumed menstruation, and one achieved clinical pregnancy, defined as a pregnancy that is confirmed by ultrasound as well as a fetal heartbeat.
Although more research and larger studies are needed, these early results regarding the successful resumption of ovarian function offer hope to women in early menopause who may be able to pursue pregnancy through in vitro fertilization using their own eggs.
Results are published in the article “Resumed ovarian function and pregnancy in early menopausal women by whole dimension subcortical ovarian administration of platelet-rich plasma and gonadotropins.”
“This pilot study investigating the use of platelet-rich plasma and gonadotropins injected into the ovaries of women with early menopause highlights the promise of regenerative medicine in restoring or prolonging fertility. Additional studies conducted prospectively and involving large numbers of women are needed to determine whether this is truly a viable option for women with early menopause hoping to achieve pregnancy using their own eggs,” says Dr. Stephanie Faubion, NAMS medical director.
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The City Losing Its Children to H.I.V.

Listen to This ArticleAudio Recording by AudmTo hear more audio stories from publishers like The New York Times, download Audm for iPhone or Android.One day in February 2019, Nazeer Shah carried his 1-year-old daughter, Eman, into a medical clinic. The doctor there, Imran Arbani, was immediately alarmed: The girl was limp and lethargic, her head flopped over on her father’s shoulder. Her breathing was shallow and fast. She was asleep, hard to rouse, except when she woke to cough. She drooled from her mouth. Her tongue was covered with a thick white coating, which Arbani recognized as thrush, a condition that usually indicates a weakened immune system. At around 11 pounds, she was frighteningly underweight.Shah told the doctor that Eman was born healthy and was well until three months earlier, when she began having diarrhea daily. Her weight dropped precipitously; she spiked fevers regularly. Every day she seemed worse than the day before. Shah handed the doctor a green plastic bag filled with assorted syrups and pills — more than a dozen different medications. These were all the things she had tried, he explained. Nothing helped. He had taken her to several doctors here in Ratodero, an impoverished city in southeastern Pakistan, and to specialists in Larkana, a city roughly 20 miles to the south. He couldn’t get any clear answers.Shah lives close to Arbani’s clinic but was initially hesitant to take Eman to him because his specialty was urology. Arbani, however, is used to practicing family medicine as well. “A doctor is a doctor,” he says. “The people do not treat doctors who are specialists as specialists. I deal with a lot of general problems too.” Arbani, who has thick, expressive eyebrows and speaks in quick, forceful clips, told Shah that he wanted to test the girl for the human immunodeficiency virus.This article was supported by the Pulitzer Center.“Doctor, are you joking, saying she might have H.I.V.?” Shah replied. “How is it possible?” But it was seemingly the only test that had not been done yet, so Shah drove Eman on his motorbike to a local laboratory, where a health care worker pricked her finger for a drop of blood. They waited outside for half an hour, until Shah was given a slip of paper. “Weak positive,” it read.“I was still confident at that point,” Shah told me. “It could be negative.” He took the results to Arbani, who suggested that Shah send another test to a satellite lab in Larkana run by Aga Khan University Hospital in Karachi, one of the country’s premier academic medical centers. Afterward, Shah returned to Arbani’s clinic so that together they could look at the results, which were available online. When they saw the word “reactive,” Shah began to weep. Arbani counseled him on the next steps and advised that Eman go to Karachi, more than 300 miles away, because the closest H.I.V. treatment facility, in Larkana, was set up to treat adults. Shah, who had a stable bank job at the time, was able to scrounge up the 2,400 rupees, or about $15, for his family’s bus fare. (The average household income in Pakistan is around $260 a month; most in Ratodero survive on far less.) He spoke to a close friend and told him about his daughter’s condition. The response shocked him.“My kid already has H.I.V.,” Shah’s friend said. Eman, it turned out, was not the first young child infected with the virus in Ratodero, where more than 300,000 people live. Shah’s friend’s son received the same diagnosis two years before. In each case, the parents tested negative for H.I.V.In 2020, about 2.8 million people worldwide under the age of 20 were living with H.I.V.; over half of them were younger than 10, according to UNAIDS, the United Nations H.I.V. program. In a vast majority of these cases, the infection was acquired through vertical transmission, meaning an H.I.V.-positive mother passed the virus to her child during pregnancy or delivery or while breastfeeding. It was unusual that these two children in Ratodero had H.I.V. when their parents did not. Nor did either child have a chronic disease that would require rounds of blood transfusions or routine kidney dialysis, which could possibly expose them to blood-borne illnesses. The two previous major outbreaks in the area — one among drug users who used needles and another among patients at a contaminated dialysis center — involved higher-risk populations. After Eman’s diagnosis, Arbani began testing many more of the sick children he saw for H.I.V. Within a matter of months, he had identified 14 pediatric patients with H.I.V. All of them were younger than 10. Sarah Caron for The New York TimesNazeer Shah and his daughter Eman, who is now 3 and has H.I.V.Sarah Caron for The New York TimesThe big three infectious diseases that plague the world — H.I.V., tuberculosis and malaria — cause more than 2.3 million deaths a year, disproportionately in poorer countries. Until the coronavirus pandemic, though, the overall trend with these diseases was a cause for optimism. Two-thirds of the world’s 38 million H.I.V. patients are now getting treatment, and their expected life spans have been lengthening significantly in recent years, as doctors have increasingly figured out how to forestall acquired immunodeficiency syndrome, or late-stage H.I.V. At the same time, infection rates have been in decline, thanks to advocacy, well-directed funding and smart public-health efforts: New H.I.V. infections have been reduced by nearly a quarter since 2010.Remarkable advances have been made against malaria too over the last two decades. Deaths caused by the disease have dropped by 44 percent. In 2019, the first malaria vaccine was distributed in sub-Saharan Africa. This is also the region of the world where the largest gains have been made against H.I.V. And while the global campaign against tuberculosis has had less success — in large part because of the emergence of multiple-drug-resistant strains of the bacterium responsible for the disease — progress has nevertheless been steady, with a drop in deaths of nearly 15 percent over the last five years. Now another virus has been threatening to undo this progress. Over the course of barely a year, the coronavirus has infected more than 120 million people worldwide, directly claiming the lives of more than 2.7 million. Coronavirus infections have disrupted medical services, scrambled drug-supply chains and necessitated the redeployment of public-health staff. According to the Global Fund, an international organization that finances health initiatives, about 75 percent of H.I.V. programs have already been moderately or severely disrupted.This has dire implications: UNAIDS estimates that even a six-month interruption of antiretroviral therapy for 20 percent of people would result in more than 110,000 additional deaths. In a September study in The Lancet Global Health, researchers modeled the impact of Covid-19 on H.I.V., tuberculosis and malaria. Over the next five years, in low- and middle-income countries where these diseases are highly prevalent, deaths could increase up to 10 percent for H.I.V., 20 percent for tuberculosis and 36 percent for malaria.For these reasons, Mishal Khan, a policy analyst at the London School of Hygiene and Tropical Medicine who studies Pakistan’s health system, says she doesn’t want “everything to be about Covid, because it’s not like the other issues will go away.” They’ll just “get neglected,” she adds, because even infectious diseases that have been “taking lives for decades” haven’t been tracked as closely as Covid-19. The diversion of resources from H.I.V. and other health conditions to the pandemic inevitably affects the most vulnerable. As António Guterres, the U.N. secretary general, warns in a UNAIDS Global Report, H.I.V. and Covid-19 have each exposed “our world’s fragilities — including persistent economic and social inequalities and woefully inadequate investments in public health.” Rabia, 5, Gulshad, 5, Sarif, 4, and Ilyas, 3, in February. The children, all H.I.V.-positive, live in a village outside Ratodero.Sarah Caron for The New York TimesIn Pakistan, H.I.V. numbers have long been trending in the wrong direction. The most recent data indicate that only 21 percent of those infected with H.I.V. in Pakistan are aware of their status. According to UNAIDS, there are an estimated 190,000 H.I.V.-positive people in the country, and only 12 percent of them receive treatment. As a result, there has been a 385 percent increase in H.I.V.-related deaths in Pakistan since 2010. Sub-Saharan Africa, in contrast, has had a 45 percent decline over that same period. Pakistan has one of the fastest-rising rates of infection in Asia and the Pacific.Why has there been a resurgence of H.I.V. in Pakistan even as it has declined elsewhere? Much of the reason is money — specifically, the lack of consistent and equitable government spending on health. According to the World Bank, just over 3 percent of the country’s gross domestic product goes toward health, one of the lowest such allocations in the world; its neighbor Afghanistan devotes nearly 10 percent. Per person, less than $45 is spent on health care annually in Pakistan, which relies heavily on foreign aid; in the United States, which has the highest per capita health care expenditures in the world, the amount is around $10,600. Life expectancy for the average Pakistani is 67 years, more than a decade shorter than it is for Americans. Pakistan, one of three countries that has not eradicated polio, also currently bears some of the heaviest burden from tuberculosis, at least in part because being H.I.V.-positive increases the risk, by roughly 20-fold, of developing the disease. Yet many poorer countries manage to have better health outcomes than Pakistan by focusing on primary care and strengthening their public-health capacities. Allocating resources strategically and prioritizing hard-to-reach areas and marginalized groups can help ensure that access to services is not determined by geography or income. Active disease surveillance and prevention can blunt outbreaks, or at least stop health systems from becoming apathetic and dysfunctional when crises surface.The vexing failure that can follow from neglecting to take these steps is nowhere more visible than it is in Ratodero. As of Nov. 30, an astonishing 1,132 children in the city and its environs were H.I.V.-positive, most of them under age 13. To put this in perspective, the equivalent figure for the entire United States is less than 2,000; the American population, 330 million, is a thousand times that of the Ratodero metropolitan area. (An additional 408 adults have also tested positive for the virus there.) The numbers in Ratodero are certainly higher now. Imran Arbani and local journalists compiled a list of children who have died from H.I.V. since the outbreak began; 48 is their current tally.As the end of the pandemic seems to be coming into sight, the riddle of H.I.V. in Pakistan is a crucial one to unravel in order to understand how to resume progress on global health in the post-Covid era. The previous headway made against some of the world’s deadliest infectious diseases isn’t guaranteed to continue. Even in favorable socioeconomic conditions, drugs and programs can’t make up for a weak health care infrastructure. The pandemic has strained, if not wrecked, many countries’ health systems and left many people poor and vulnerable — a reality that Ratodero has long been reckoning with. Mohammed Iqbal outside the hospital in Ratodero with his children Zaheer, 8, and Zameeraan, 5, while they waited for H.I.V. medicines. Iqbal’s 11-year-old daughter is also H.I.V.-positive.Sarah Caron for The New York TimesShah and his family arrived in Karachi in March 2019, after a seven-hour, overnight trip, and took Eman to Civil Hospital, the only public hospital in the city with a pediatric H.I.V. treatment center. By then, Shah says, Eman’s struggles to breathe had worsened. He thought she would be admitted to the hospital immediately. Instead, they were told she wasn’t sick enough and were sent away. On the day I visited, last March, the hospital was chaotic and overcrowded, with patients waiting outside in amorphous lines. I saw several patients — one with a broken femur, others who looked profoundly dehydrated — in makeshift cloth stretchers propped up with sticks hoisted by family members. They, like the patients who were able to stand, waited hours to be tended to.The hospital’s pediatric H.I.V. treatment center is tucked in the back, in a concrete building. Iqbal Soomro, the doctor who has been running the center for more than a decade, didn’t remember the particulars of Eman’s case. But he showed me her chart, where he had checked the box “unknown” to indicate how she had been infected. Each month, he and his staff compiled these cases and sent them to the Sindh AIDS Control Program (S.A.C.P.), also in Karachi. (Karachi, Pakistan’s most populous city, is the capital of Sindh Province, which also includes Ratodero and Larkana.) “It is my duty to give report,” he told me. “After that, I don’t know.” For five days, Shah returned to the hospital every morning with Eman. They were turned away every time, he says, and Eman got sicker. Finally, on the sixth day, she was admitted to the hospital. She was put on oxygen, but she was not treated with any antiretroviral medicines, according to Shah, who grew increasingly concerned and called Arbani. The doctor told him that his daughter should have already started taking H.I.V. medicine. Shah questioned the hospital doctors but, he recalls, was met with resentment. In Pakistan, patients have little power. “Patients are intimidated, and doctors exploit it to the fullest,” Arshad Altaf, a Karachi-based public-health and injection-safety expert who has worked for the World Health Organization, told me. “If a patient questions the doctor, she or he will snap back with a reply like, ‘I know better than you’ or ‘Am I the doctor or you?’ and this largely keeps the patients quiet.”Desperate, Shah discreetly sought out a hospital pharmacist to see if there was another way for him to get antiretroviral medications for his daughter. The pharmacist suggested that he get another opinion, at Aga Khan University Hospital, the private academic medical center across town. There, patients pay out of pocket for every consultation and hospitalization; the cost of such top-level private medical care is prohibitive for many Pakistanis who need it. Only the H.I.V. medications themselves are free, largely financed by international organizations. Shah borrowed some money and took Eman to Aga Khan. On the day that she was admitted into the intensive-care unit, she was started on antiretrovirals. Her CD4 count, which measures the strength of the immune system, had fallen to 90, an often fatally low number. Back in Ratodero, Arbani began to worry. He had been referring cases to the H.I.V. centers at the hospitals in Larkana and Karachi and anticipated that they would prompt an investigation. But weeks passed without any word from public-health officials. When he finally received a call related to the outbreak, in the third week of April, it wasn’t from someone in the government. A reporter in Karachi named Yousif Jokhio was calling: A relative had connected them, and he told Arbani that his cousin’s child, who lived in Ratodero, had died of H.I.V. earlier that day. “I was shocked,” Jokhio says. “How is it possible that a 2-month-old is H.I.V.-positive when his parents are negative?”Arbani was relieved to hear that somebody was finally asking questions. He had kept careful records for the previous two months, and now he shared many of his files willingly. At noon on April 24, two days later, Jokhio’s station broke the full story about the cluster of H.I.V.-positive children in Ratodero. About an hour later, another TV station did the same. Its reporter, Gulbahar Shaikh, who was from Ratodero, says he began investigating after seeing a Facebook post by Nazeer Shah. After the two televised accounts, word of the outbreak quickly spread across the region and soon the country. Dr. Imran Arbani examining a 20-year-old patient with H.I.V.Sarah Caron for The New York TimesThe Sindh AIDS Control Program should have been actively engaged in disease surveillance, which would have caused it to investigate the early cases in Ratodero, but the program — and the rest of the government — seemed to learn about the outbreak at the same time the world did, from news reports. Altaf Soomro (no relation to Iqbal), who directs efforts to teach the community about H.I.V. for a nonprofit called Bridge, had worked for the Sindh AIDS Control Program; he is now critical of it. “S.A.C.P. is the main program who is responsible for covering all these things” related to the H.I.V. outbreak in Ratodero, he told me. “If they had worked effectively, no such outbreak would’ve happened.” (In July, after government restructuring, the program was absorbed by the Sindh health department.) The negative media attention generated intense public pressure on provincial health officials to act. The W.H.O. pronounced the situation in Ratodero an emergency. As television crews descended on the area, the government prepared to rapidly deploy doctors and epidemiologists to the area. H.I.V. doctors in the public hospitals went to Arbani’s clinic and demanded to know why he had gone to the news media first. A pathologist who handled positive tests told me that he was pressured by government officials to play down the number of them; he refused and left his position.Some government doctors confronted Arbani on the grounds that he had violated patients’ privacy when he gave their names to journalists. While the TV broadcast did not show any photos or identify any patients, Arbani had handed over a list of names to Jokhio. As a longtime journalist reporting on the government, Jokhio viewed this as necessary to ensure accountability. “Without them, the government would bury everything,” Jokhio told me. “Sometimes you have to inflict injury to get to the cure.” (Subsequent local news reports did reveal the names and faces of patients and their families.) In my time there, many parents were eager to have their stories made public, bringing out medical records and sharing their experiences with me. Others followed me to ask why I hadn’t inquired about their infected children.Within a week after the news broke on TV, the provincial government sent a group of experts to Ratodero to respond to the outbreak. Many of the infected children had visited a physician named Muzaffar Ghanghro, an inexpensive doctor in town with a practice focused on children. Ghanghro was forced to be tested for H.I.V. When the results reportedly indicated that he had the virus — possibly contracted from two blood transfusions he received after a car accident, according to local doctors — some health officials publicly rejoiced; they were relieved to have found what seemed to be the culprit, eager to imply that his positive test result somehow meant that he was intentionally infecting children with H.I.V. (Ghanghro denies that he is H.I.V.-positive.) The news of his H.I.V. status was immediately televised. The police arrested him, and Ghanghro was branded the sole cause of the outbreak. “To settle down the pressure, the government had to do something to show they’re holding someone responsible,” a representative from UNICEF, the U.N. agency for children’s affairs and emergencies, told me. As news of the arrest circulated, families of infected children made public accusations against Ghanghro. Out of caution, Gulbahar Shaikh, the local TV reporter, decided to have his children tested too. He was shocked when the results came back positive for one of them, his 1-year-old daughter Rida. She was sent to the government hospital in Larkana to get a chest X-ray to screen her for tuberculosis; she waited two days for the X-ray. Then someone at the hospital told Shaikh that there was no pediatric H.I.V. treatment there. He sold his wife’s jewelry to pay for Rida’s medical care in Karachi. “If they are doing this to me,” Shaikh told me, “how will it be for the common person?” Rida, Shaikh’s daughter.Sarah Caron for The New York TimesA health system under strain collapses when it’s stressed. Not everyone feels it when it gives way. But it almost always throws into free fall the most defenseless first: children, the poor, the uneducated, the marginalized. The failure to prevent an outbreak — and to recognize and control one after it starts — is acutely diagnostic of the broader chronic problems afflicting a country’s health system, fluorescing its deepest injustices. Fatima Mir, who runs the pediatric H.I.V. clinic at Aga Khan University Hospital in Karachi, was one of the doctors who went to Ratodero to help with the emergency response there. In March, about a week before the coronavirus was declared a pandemic and as Covid-19 was beginning to surge across my home, New York, I visited her at Aga Khan. It’s a breathtakingly beautiful place: Lush palm trees surround its courtyards, and ivy climbs up its buildings, which have marble floors and teak ceilings. Valet-parking staff members greet visitors. The hospital is a calm oasis in a hectic city. Mir, a short woman who is warm and effusive — but stern when she needs to be, punctuating her convictions with curse words — led me to her office, where she has a poster of a woman in a superhero outfit, captioned “Ms. Dangerous.” The most basic requirements for a center were absent when she got to Ratodero in May 2019: That first morning, she explained, she didn’t even have a chair to sit on. She went to the store to buy notebooks to make rudimentary prescription pads. She weighed the children herself. A colleague began seeing children in an open-air tent, while Mir borrowed two rooms in an adult clinic to treat patients, amid a crowd of desperate parents. “I washed my hands in the morning in my hotel, and I washed them at night when I came back,” she said. “I did not wash my hands even once between the 80 patients” she saw each day, because no soap or clean water was available. Reporters roamed freely, listening in on people’s conversations, taking note of which families had children who tested positive. It was bedlam. “We were hit by an atom bomb,” she said. Mir was tasked with training public-health doctors from the polio-vaccine program to become pediatric H.I.V. specialists in two weeks. She was shocked at how little clinical experience they had. “They were not very used to even touching patients,” she recalled. Trying to teach them how to examine a patient with H.I.V., to look for specific physical findings, “was a disaster.” They were the equivalent of first-day graduates from medical school. So she simplified everything as much as she could. For instance, she told them not to treat tuberculosis at the same time as H.I.V. because the two medication regimens could get too complicated. After three months, a formal pediatric H.I.V. treatment center finally opened in Ratodero, housed in the public hospital. It was staffed by Mir’s trainees, supported with emergency funding from international agencies.Arbani continued to be the eyes and ears of the community, searching for cases to refer to the new facility. He was convinced that some of the negative test results for the children he was seeing were false. His clinical instincts told him that these children had too many symptoms consistent with H.I.V. — weight loss, persistent coughs and diarrhea — and where there was one case of horizontal transmission, there were likely to be more. He also had a hunch that the public labs weren’t as accurate in their testing as the private ones, so he sent patients to Aga Khan’s satellite labs in Larkana for confirmation, as he had done with Shah back in February. Arbani has turned out to be right. Since Eman’s H.I.V. diagnosis, he has identified a dozen cases of conflicting results — that is, the parents were told their children didn’t have H.I.V. when, in fact, they did. For some of them, this significantly delayed treatment and might have led to preventable deaths. Perhaps spurred by all the media attention, Pakistan’s national Ministry of Health sent an international team, with support from Aga Khan University, U.N. agencies, the W.H.O. and the Centers for Disease Control and Prevention in the United States, to Ratodero to thoroughly examine the outbreak. They uncovered a multitude of unsafe medical practices in the area, similar to what Mir discovered. Based on interviews with hundreds of parents, almost every child who tested positive had also received an injection of some kind in the previous year. What’s more, H.I.V.-positive children had had roughly three times the number of injections compared with their virus-free peers. Investigators found that needles and intravenous lines were being reused, despite a 2011 law mandating the production and stockpiling of single-use disposable syringes. Pakistan has among the highest number of unsafe injections in the world, according to several international studies. This grim ranking is in part an inevitable byproduct of a fragile health system, but the reasons are complex and interrelated, driven as much by socioeconomic factors and long-held cultural beliefs as by a lack of government investment and oversight. The standards for preventing and controlling infection are not adequately taught or enforced in undergraduate medical education in Pakistan; in one survey, over 80 percent of medical students responded that they needed better training. As a result, hand-washing, the use of disposable syringes and the proper discarding of needles and sharp instruments aren’t always practiced by medical providers. Because the oversight of medical education in Pakistan isn’t very strict, the recent proliferation of private medical schools is troublesome. These institutions set their own admission and graduation standards and can be highly variable. Exact numbers are unclear, but it seems there are at least 70 medical colleges registered, with possibly an additional 50 or so that are not yet registered or are operating under the radar, according to Mishal Khan, the London School professor. What’s more, Khan says, requiring continuing medical education to learn, say, the latest standards for infection control or how to diagnose new diseases is not customary in Pakistan. And unfortunately, in places as poor as Ratodero, health providers may resort to reusing medical equipment to cut costs.The shortcomings aren’t limited to allopathic medicine. Many Pakistanis seek care from homeopathic providers and chiropractors. Pharmacists and technicians also practice in ways they’re not qualified for, as do others who have no training whatsoever (all of whom the Pakistan authorities call “quacks”). The regulatory oversight of these alternative health care providers is uneven, at best. Though they are not licensed to do so, some give patients shots and intravenous medications. A study in 2014 found that over 70 percent of health care services in Pakistan are provided by the private sector; this may be, in large part, because public facilities often close their doors at 2 p.m. In fact, many of these government-employed doctors go from their jobs in the morning to their own private clinics in the afternoons. As a whole, government-run facilities also do not serve poor, illiterate patients very well. To attract and retain their patients, private doctors and quacks alike have incentives to provide injections even if they’re superfluous, because patients might otherwise think they haven’t been treated effectively. As such, Pakistan has one of the highest injection rates in the world, with research showing that people get at least five to eight shots a year, while some studies conclude that the number is closer to 14. Nearly 95 percent of these, according to the national government, are considered medically unnecessary. Unlicensed blood banks are also known to inadequately screen blood. Poor parents may forgo their own health care, but they’re still inclined to take their children to the clinic, no matter how limited their funds.The problem is pervasive. “Except for a handful of health care facilities in the country, there is hardly any concept of infection prevention and control,” Arshad Altaf, the public-health expert, told me. As a result, Pakistan bears the second-highest global prevalence of hepatitis C, another blood-borne pathogen. In Ratodero’s district, the Sindh HealthCare Commission has been made responsible for finding and shutting down facilities that aren’t properly licensed or don’t adhere to standards of care. The commission was created in 2017, though it didn’t actually start operating until 2018 because of insufficient funding. When the H.I.V. outbreak in Ratodero became widely known, the commission went around and closed noncompliant and illegitimate facilities around the area. In total, it put more than 300 practices out of business, including several blood banks. It also detected black markets selling reused needles. “We diverted all our forces to respond to the Ratodero incident,” Minhaj Qidwai, at the time the chief executive of the Sindh HealthCare Commission, told me. By December 2019, health officials thought that the source of the H.I.V. outbreak was well controlled.Sarah Caron for The New York Times Household trash and waste from medical clinics are regularly discarded in a central square in Ratodero where children play.Sarah Caron for The New York TimesPrivate clinics are scattered among the shops and food stalls on nearly every block in Ratodero, their homogeneous fronts no different from those of the commercial stores. When I visited the area in February last year, it had been two months since unlicensed facilities had supposedly been shut down. Walking on dusty dirt roads under an unforgiving sun, I dodged goats and donkeys and motorized rickshaws. Festive music spilled from the market stalls, accented by the merchants’ shouts. Children darted in and out of the alleyways. I visited a dozen or so clinics. Most of them had no place for hand-washing. The two barbershops I stopped into each indicated that they reused razors.In one clinic, a tall man in an olive-green kurta with a stethoscope around his neck was examining a baby. As soon as I walked in, he put the baby down and dropped his stethoscope. Though I didn’t ask what he was doing, he was quick to let me know that he wasn’t examining the patient but was simply checking her temperature. I looked around. No thermometer was in sight. I asked him where the doctor was; he said he would be back in five minutes. When I told him I would wait outside, he told me that the doctor wouldn’t return for at least an hour. Better to make it 7 o’clock, he advised. I returned a few minutes early. A steel door was pulled down; the clinic had closed. It remained that way for the rest of the evening, even though it was supposed to stay open until 9. Many such clinics were run by those without full medical qualifications. The man in the green kurta with the stethoscope probably had a “medical dispenser” degree, whose requirements can vary by school — they might consist of scoring at least 45 percent in one’s high school science classes and then completing a one-year course, for example. The doctors weren’t actually on site; they had lent their names to the clinics and benefited from the profits. Patients and their families didn’t know better. “Someone puts a stethoscope around the neck and sits in a room in a community, and he or she becomes a doctor,” Altaf told me. Even those with medical degrees often didn’t follow the proper measures to avoid infections. At best, their methods were opaque. The providers regularly went behind lecterns or disappeared into separate rooms to prepare injections and IVs, making it impossible for patients and their families to see what was happening. At worst, needles and IV cannulas were openly reused. When I asked on-site providers about their operations, they told me that patients are responsible for buying their own needles and IV sets from the pharmacy. Yet there were boxes of such equipment in the facilities themselves. I saw this in practice, too: As a boy, who was around 5, got an IV drip through his left hand in one clinic, his doctor told me that his mother had bought the IV herself from the pharmacy. But when I asked her about this later when the doctor wasn’t around, she told me that he had supplied everything.Based on what I saw, the mishandling of medical equipment seemed to be prevalent. Used needles were littered about one health facility, on filing cabinets and windowsills. Residual blood was visible in some of them. The doctor on site quickly threw several needles out the window, telling my translator in Sindhi that he didn’t want me to see them. He also informed me that he had disposed of the syringes in designated sharps bins, which are hard plastic or steel containers with locked tops. But none were visible; he told me they had been sent to the government hospital in Larkana for incineration. I didn’t see any gloves either; the doctor said he had discarded all of them. Nebulizer masks, which can be contaminated with respiratory droplets, were reused here, as in other facilities I visited.At a government hospital in Larkana, I watched as a nurse left a needle uncapped after preparing medication in the pediatric unit. Then she tossed it, tip still exposed, into a regular wastebasket. I didn’t see any sharps containers. Outside, I asked a cleaner how the hospital deals with trash. He walked me past the hospital’s front gate and showed me the garbage lined up around its perimeter. There were exposed needles, IV cannulas and dirty nebulizer masks everywhere. An incinerator was nearby, but it wasn’t in use. (The W.H.O. has since donated new incinerators, but the pandemic delayed their installation.)As an emergency-room doctor, I have provided medical care overseas in all sorts of ghastly environments. Still, I was shocked here. Even in impoverished, war-drained countries in sub-Saharan Africa, I was kept to the strictest of infection-control standards as a medical student. Nurses in the operating and labor and delivery rooms had eyes in the back of their heads, ready to admonish anyone who broke protocol. In an H.I.V. ward in South Africa, I was startled by the lacerating words of a fellow student, a local woman, as I clumsily handled a needle. She warned me that no matter how rushed I was, this task can’t be compromised. It’s the first lesson we learn here as students, she explained.Syringes with built-in safety closures that easily slide forward to cover the needle are common in American health facilities, but even at Aga Khan, these aren’t available. At best, the plunger gets locked, so the syringe can’t be reused. When I went to several pharmacies, where these needles are dispensed, and asked about proper disposal, I got awful advice. One pharmacist bent the needle to 120 degrees. “This is what we do,” he told me. The sharp tip was still exposed, obviously. “In the sewer, in the street,” another pharmacist said when I asked him where to discard the needle, before tossing it out the window without looking. I watched the needle float in a puddle of open sewage. Around the corner, children skipped down the street.At the time, Rajesh Panjwani was the Sindh HealthCare Commission’s deputy director of inspection for the Larkana area, which includes Ratodero. I managed to see him. He shared an office with Faraz Hussain, an administrator; their desks were at right angles to each other. “All the hospitals are using the safety boxes,” Panjwani assured me, referring to sharps bins. I told him that was not what I saw, but he disputed my characterization. We went back and forth until he had to take a phone call. I didn’t even know Hussain was listening, as he was typing briskly on a large desktop computer, but now he spoke up. “You are telling 100 percent truth about the government hospitals,” he said to me.Later, Panjwani told me that he had inspected many clinics in the area and that they had safety boxes available. I said I hadn’t seen a safety box in any of the dozen or so clinics I visited. At this point, Hussain said something to Panjwani, and they began to argue in Sindhi. My translator quietly said to me, “Hussain is saying: ‘She’s telling the truth. Please admit the truth. There’s no safety boxes at the clinics.’” Everything, it seems, is always someone else’s job. Aftab Ahmad, a doctor who was in charge of monitoring and evaluation at the Sindh AIDS Control Program, blamed the district health office for the outbreak. “There is some denial, you are right,” Ahmad said. “People are not completely doing what they ought to do.” As for the Sindh HealthCare Commission, while it can order a clinic to be sealed, it looks to the police to enforce the order. The commission considers its job done when it has made its recommendation to close clinics with violations; the commission doesn’t consider itself responsible for actually shutting the facilities down or making sure they stay closed. The cruel dilemma, though, is that without these private health spaces, many people in Ratodero and other remote areas in Pakistan wouldn’t have access to any health care. For the poor and uneducated, the choice is usually between terrible care or no care at all. A general health clinic in Ratodero in February.Sarah Caron for The New York TimesUzma Sheikh had just begun to babble “aba” — “dad” in Sindhi — at her father, Nisar Sheikh, when she fell ill in the summer of 2019. Though they didn’t have money to pay for the visit, Uzma’s parents took her to Arbani’s office one August evening that year. He saw her free of charge, then sent her to get an H.I.V. test at a laboratory because the new treatment center in Ratodero was closed. The result came back positive. At the center the next morning, the test was repeated and was negative. Arbani didn’t believe the result; Uzma looked very ill and had all the telltale signs the other children had. He gave $10 to her father to take her to the Aga Khan lab; that test, once again, came back positive. Uzma’s parents then took her back to the treatment center, but because its own test had been negative, the doctors refused to treat her. “We’re illiterate people,” Sheikh said. “We don’t know how to talk to people at the hospital.” They returned home. Less than a week later, Uzma died. Inside a dark, mud-floored hut held up by crumbling bricks and a thatched roof, I sat on a straw cot surrounded by chickens. A small open fire on the ground heated up a pot, from which thick, throat-burning smoke poured out. Uzma’s parents rummaged about their one-room home, pulling out photos of their daughter. The girl had enormous eyes and ears that stuck out.Sheikh wanted to show me her grave. He led me across dirt fields, making turns at unmarked spots until we came upon a small hill, a mound of dirt with a line of gray stones on top in the shape of a child-size coffin. He gazed to the horizon, his face defiant. “We’re angry at times,” he said. “But life just goes on.”Around the time of Uzma’s diagnosis, another girl, Saba Junejo, also tested positive for H.I.V. She, too, was unable to get medications from the treatment center, though for different reasons. I visited her home, which was in one of the villages surrounding Ratodero, far from the city; we drove past water buffalo herds, grass fields and a river, making three wrong turns before arriving. An extended family of six adults and 10 children lived in the two-room home, which had only one tiny window. A lone light bulb flickered weakly. Saba’s parents told me they were informed by staff members at Ratodero’s treatment center that it was out of medications and that they should come back in a month. Back home, Saba continued to spike high fevers and stopped eating. For the next several days, the family tried to borrow enough money to pay for transportation to take the girl to Larkana. But on the third day, Saba stopped breathing. When I was there, her 3-year-old brother was asking every day, “Where is my sister?” The family has run out of money. As farmers, they would have put their savings toward next year’s harvest, but they paid for Saba’s medical expenses instead. For now, they are without income. Saba’s mother, Safiyah, has one pair of gold earrings, which she tried to use to get a loan. “If Saba had lived, she might be walking today,” Safiyah said, shaking her head.Zahid Meerani, a shopkeeper, knows her grief all too well. He called out to me when he saw me going around the market — he wanted to make sure I publicized his family’s suffering. “My boy was the first to die from this outbreak,” he told me. His son was 2. “I want to say to the government: ‘My boy is dead. Please save the other kids.’” Zahid Meerani with his son and wife. She is holding photographs of another son, Ghulam Nabi Meerani, who died of H.I.V. when he was 2.Sarah Caron for The New York TimesIn many ways, the public-health system in Ratodero is like public-health systems everywhere: Its workers are understaffed, underpaid, disillusioned. The work is tedious, and the reward for success can be invisible. After all, the public doesn’t realize when disease is prevented; it only knows when it’s not. Governments need to keep an accurate count of cases, track where and how a virus is circulating and coordinate a response to choke its spread — or at least slow it down. Even the most heroic efforts by individual doctors and nurses aren’t substitutes for government leadership and public-health action. When they’re inadequate, preventable outbreaks erupt, the difficult-to-control turns impossible. Diseases unfurl. People die. It’s easy to blame one person, but an entire system has to fail for this number of children to contract H.I.V. Muzaffar Ghanghro, the pediatrician, spent nearly two months in jail before the charges of doing intentional harm to his patients were dropped, though it’s quite likely that he, as many medical providers do, reused supplies and didn’t strictly adhere to sanitation practices. Some public-health officials have since acknowledged that the doctor was scapegoated. “Someone has to blame someone,” the district health officer said.When I called Ghanghro, he said he was in Karachi, though I soon found him outside his home, not far from the center of Ratodero. He told me he didn’t want to talk, yet he was also determined to clear his name. He was agitated, his speech frenzied, perspiration collecting on his forehead. “They created a whole story just to blame me,” Ghanghro said. “All of the government wanted to transfer responsibility to one person because people needed an answer, so they just accused me.” In fact, he said, some families blamed him for their children’s infections, even if he never cared for them. He maintains that he has not done anything wrong and adamantly denies his H.I.V. diagnosis. But he also asked rhetorically, “Even if a doctor has the disease, won’t he still be allowed to practice?” Sikander Memon was the head of the Sindh AIDS Control Program during my trip to Pakistan. Memon, a short, balding man with a very thick beard, was initially suspicious of me. To try to put him at ease, I told him that I was aware that it could be difficult to work in a place like Ratodero. “This time is not that time,” he replied. He was clearly upset that I had visited the area without telling him first. “Without seeking permission of mine, you were there yesterday,” he said. “I’m not informed by anybody that you’re going to Larkana, and I would not allow anybody permission to give you information about H.I.V. If you got information, I will punish them.”Those on the ground acknowledge that there was a shortage of medicines, particularly early on, but Memon denied that. “There was not a single day that a patient came to our center and did not get medicine,” he insisted. I mentioned a three-month gap when patients could not be tested for their H.I.V. viral load. “A gap of three months is not a big deal,” Memon replied. At one point, exhausted by my questions, Memon cut me off. “Look, this is not our responsibility to keep alive all the people by giving them medicines,” he said. “It’s up to Allah.” Toward the end of our meeting, Memon received an urgent call. He was being moved to the coronavirus program. Pakistan’s first case had been detected in Karachi the day before. He was done with H.I.V. As we walked out together, Memon seemed relieved to be moved to another disease unit and recommended that I talk with Azra Pechuho, the Sindh minister of health and population welfare.Wearing a peach flower-embroidered silk sari, Pechuho greeted me from behind a wide desk in front of lofty windows; her office was spacious, with plush cerulean velvet couches framing an elegant sitting area. She immediately started listing her staff’s accomplishments and their upcoming initiatives. Eventually, the discussion circled to the pediatric H.I.V. outbreak in Ratodero. When I asked about Zahid Meerani’s deceased son and other victims, Pechuho denied that their deaths were related to H.I.V. When I challenged her, questioning why their cases weren’t investigated after they sought care for H.I.V. in government hospitals, Pechuho countered in anger and, her voice rising, blamed the lab in Ratodero for the media revelations. A suited man had slipped in during our meeting and was sitting on one of the couches. Pechuho shouted at him to grab files from the government hospitals. He looked confused and didn’t know what to do next. Pechuho then banged on her desk with her fist. She ordered her assistant to escort me out immediately. Last June, accounts in the Pakistan news media noted, the government stopped putting out reports about test results — until it finally released one on Nov. 30, the eve of World AIDS Day. Case counts have not been updated since then. A majority of residents in the Ratodero area have yet to be screened.Imtiaz Jalbani, who lost two children to H.I.V., with his daughter Kaneez, 3, and his son, Ali, 7, who are H.I.V.-positive. A nephew with H.I.V. lives with the family.Sarah Caron for The New York TimesThe family of Imtiaz Jalbani, a laborer, has suffered as much as any from this outbreak. At its onset, he had five children. He lost two of them to H.I.V., and two more are H.I.V.-positive; both he and his wife, Zulekhan, are negative. When I saw them in Ratodero, she had just given birth to a girl, who, fortunately, remains uninfected. Jalbani also has a 2-year-old nephew with H.I.V., whom he now considers his son, after he moved in with them — he told me the boy’s parents preferred that he be kept separate from their other children. Jalbani worries endlessly about his three H.I.V.-positive children. “My kids are like the living dead,” he told me. “We don’t believe in anything in the world now.” He sighed, then said: “I hope I will see grandchildren, but I don’t have much hope. They will suffer; they’re on medications for life.” Ali, his oldest son, who is H.I.V.-positive and now 7, was recovering from a respiratory illness. He jumped in when he heard his father talking about medicines. “I eat tablets, and I don’t know why,” he said, his words trailing off into a coughing fit. Every day, he said, Ali took two H.I.V. tablets in the morning and two in the evening, as well as a syrup. He also ingested iron pills because of frequent diarrhea, possibly caused by the lack of clean water. In richer countries, children’s foods, like cereal, are often fortified with vitamins and minerals, which would cut down on this daily medication regimen. The ready availability of refrigeration would also allow some of their pills to be replaced by easy-to-swallow formulas.“It’s criminal,” says Fatima Mir, from the pediatric H.I.V. clinic at Aga Khan hospital. “But because people are not very aware of what has been done to them, now their child will live with a chronic condition all their lives. No matter that what we know about life expectancy on ARVs and viral suppression is good, but it could’ve been a life in which they didn’t need to take ARVs every day and constantly go to the doctor for every diarrhea, every respiratory illness.” It’s not only the children’s physical health that worries parents but their mental and social needs, too. Jalbani had to move his family to another village because they were shunned by relatives and neighbors. Their life now is isolating, their home a tiny space encased by mud, with a few water buffalo and goats that were on loan but have since had to be returned. “It’s not just H.I.V. that’s killing us,” Jalbani said. “It’s the stigma that also kills us.” Gulbahar Shaikh, the reporter, expresses similar sentiments about his daughter. “I’m still worried about her future,” he told me. “She’s not to blame for her H.I.V. What will happen to her when she grows old and asks what was her fault in all this, getting H.I.V.? What will I reply to her?” The government had supposedly established a $6.4 million fund for the children and their families. Despite promises that they would receive the money in the spring of last year, it has yet to be distributed. In July, Ratodero’s treatment center temporarily ran out of medications, its supply of drugs having ostensibly been interrupted by the pandemic. Since then, there have been other disruptions, including, at times, patchy staffing and intermittent unavailability of H.I.V. tests. Sarah Caron for The New York TimesAbdul in February at Farhan’s grave the day after he died.Sarah Caron for The New York TimesAs more children continue to receive H.I.V. diagnoses in Ratodero, their odds of living to adulthood are running against them. After her time there, Mir has reckoned just how high. “I would be happy if at the end of 10 years,” she told me, “half of them survive.”What Mir speaks to are the merciless conditions of poverty and the decades of neglect, which no medicine can overcome. In August, Farhan, a 5-year-old boy, was found to have H.I.V. He also tested positive for tuberculosis, for which treatment was started right away. The doctor then prescribed antiretrovirals. Farhan took them every day. Still, he became very ill. In February, he was unable to breathe and had chills so severe that his father, Abdul Razaq, a farmer, thought he was having seizures. Razaq took him to a hospital in Larkana, where, after a couple of hours, the boy died. Arbani, like Mir, is not surprised. In Ratodero, he says, “there is no single month where there’s no death” from H.I.V.Eman Shah, though, eventually got better after the intensive care she received at Aga Khan. Today she is mostly healthy. “Life will never be normal again,” her father said, “but at least now life is routine.” Shah still takes her on seven-hour journeys to Karachi to get treatment at Aga Khan. He doesn’t have faith in the government facilities. When I met Eman, a little over a year ago, she was 2, and her hair was trimmed into a pixie cut, her dark, round eyes framed by long, glossy eyelashes that grazed her chubby cheeks. She was quiet but deeply curious. Shah fondly called her Emo as she toddled alongside him. He knew that he was fortunate to be one of the few in Ratodero with an education and some financial stability. When the pandemic disrupted Eman’s appointments, his relative in Karachi was able to pick up a three-month supply of H.I.V. medications for her. Recently, Shah was on the bus with Eman, on one of their trips to Aga Khan, when he texted me about the coronavirus’s devastation on the world. He fully grasped the magnitude of the human losses, the universal suffering. Yet, at last, he wrote, “We lost much and more in H.I.V.”Helen Ouyang is a physician, a writer and an assistant professor at Columbia University Medical Center whose writing has been a finalist for the National Magazine Award. Sarah Caron is a photographer based in Pakistan and Paris. She has published five books of photography, including “Le Pakistan à Vif.”

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Walking and Other Aerobic Exercise May Aid the Aging Brain

Older people with mild cognitive impairment showed improvements in brain blood flow and memory after a yearlong aerobic exercise program.Brisk walking improves brain health and thinking in aging people with memory impairments, according to a new, yearlong study of mild cognitive impairment and exercise. In the study, middle-aged and older people with early signs of memory loss raised their cognitive scores after they started walking frequently. Regular exercise also amplified the healthy flow of blood to their brains. The changes in their brains and minds were subtle but consequential, the study concludes, and could have implications not just for those with serious memory problems, but for any of us whose memories are starting to fade with age.Most of us, as we get older, will find that our ability to remember and think dulls a bit. This is considered normal, if annoying. But if the memory loss intensifies, it may become mild cognitive impairment, a medical condition in which the loss of thinking skills grows obvious enough that it becomes worrisome to you and others around you. Mild cognitive impairment is not dementia, but people with the condition are at heightened risk of developing Alzheimer’s disease later.Scientists have not yet pinpointed the underlying causes of mild cognitive impairment, but there is some evidence that changes in blood flow to the brain can contribute. Blood carries oxygen and nutrients to brain cells and if that stream sputters, so can the vitality of neurons.Unfortunately, many people experience declines in the flow of blood to their brains with age, when their arteries stiffen and hearts weaken.But the good news is that exercise can increase brain blood flow, even when exercisers are not moving. In a 2013 neurological study, the brains of physically active older men showed much better blood saturation than those of sedentary men, even when everyone was quietly resting. The greater brain blood flow in people who exercise also is associated with better scores on tests of memory and thinking than among sedentary people.But these studies generally focused on people whose brains and cognition were relatively normal. Exercise bulked up, for them, what already was reasonably sound. Far less is known about whether physical activity similarly benefits the blood flow, brains and thinking of people who are starting to experience more serious memory loss.So, for the new study, which was published this month in the Journal of Alzheimer’s Disease, researchers at the University of Texas Southwestern Medical Center in Dallas and other institutions asked a group of 70 sedentary men and women, aged 55 or older and diagnosed with mild cognitive impairment, to start moving more.They first brought everyone into the lab and tested their current health, cognitive function and aerobic fitness. Then, using advanced ultrasounds and other techniques, they measured the stiffness of their carotid artery, which carries blood to the brain, and the amount of blood flowing to and through their brains.Finally, they divided the volunteers into two groups. One began a program of light stretching and toning exercises, to serve as an active control group. The others started to exercise aerobically, mostly by walking on treadmills at the lab, and then, after a few weeks, outside on their own. The exercisers were asked to keep their exertions brisk, so that their heart rates and breathing rose noticeably. (They could swim, ride bikes or do ballroom dancing if they chose, but almost everyone walked.) The control group kept their heart rates low.Everyone in both groups worked out three times a week at first, for about half an hour and under supervision. They then added sessions on their own, until after six months, they were completing about five workouts most weeks. This program continued for a year, in total. About 20 volunteers dropped out over that time, mostly from the walking group.Then the volunteers returned to the lab for a repeat of the original tests, and the researchers compared results. To no one’s surprise, the exercise group was more fit, with higher aerobic capacity, while the stretchers’ endurance had not budged. The aerobic exercise group also showed much less stiffness in their carotid arteries and, in consequence, greater blood flow to and throughout their brains.Perhaps most important, they also performed better now than the stretch-and-tone group on some of the tests of executive function, which are thinking skills involved in planning and decision-making. These tend to be among the abilities that decline earliest in dementia.Interestingly, though, both groups had raised their scores slightly on most tests of memory and thinking, and to about the same extent. In effect, getting up and moving in any way — and perhaps also interacting socially with people at the lab — appeared to have burnished thinking skills and helped to stave off accelerating declines.Still, the researchers believe that over a longer period of time, brisk walking would result in greater cognitive gains and less memory decline than gentle stretching, says Rong Zhang, a neurology professor at UT Southwestern Medical Center, who oversaw the new study.“It probably takes more time” than a year for the improved brain blood flow to translate into improved cognition, he says. He and other researchers are planning larger, longer-lasting studies to test that idea, he says. They hope, too, to investigate how more — or fewer — sessions of exercise each week might aid the brain, and whether there might be ways to motivate more of the volunteers to stick with an exercise program.For now, though, he believes the group’s findings serve as a useful reminder that moving changes minds. “Park farther away” when you shop or commute, he says. “Take the stairs,” and try to get your heart rate up when you exercise. Doing so, he says, may help to protect your lifelong ability to remember and think.

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How Wearing a Mask Can Reduce Allergy Symptoms

Research shows that wearing masks outdoors can protect against more than Covid-19 for people who suffer from seasonal allergies.As we head into our second pandemic spring, many of us may be itching to give up our masks. But for the 19.2 million American adults suffering from seasonal allergies, there’s another reason to keep wearing your mask.While cloth and medical masks do a good job of protecting us from viral particles, studies show masks also can be effective at filtering common allergens, which typically float around in much larger sizes, making them easier to block. Pine tree pollen, for example, is about 800 times larger than the coronavirus, said Dr. David Lang, an allergist at Cleveland Clinic. Even before the pandemic, he advised patients with severe allergies to wear a mask outside, especially for prolonged activities like gardening or yardwork.Using masks to alleviate allergy symptoms can require a bit of “trial and error,” said Dr. Purvi Parikh, an allergist and immunologist at N.Y.U. Langone Health. But over all, “if there’s less pollen going into your nose and mouth, you’re less likely to have an allergy attack,” she said.Israeli researchers recently studied how much difference wearing a mask could make for allergy sufferers with mild, moderate and severe symptoms. Using data collected from 215 nurses who used surgical masks or N95 masks during a two-week period, they found that among the 44 nurses with severe allergy symptoms, nearly 40 percent experienced less sneezing, runny nose and stuffy nose when they wore either a surgical or N95 mask. Among the 91 nurses with moderate symptoms, 30 percent improved when they wore a surgical mask; that rose to 40 percent when they wore an N95. Among the 80 nurses who started the study with mild symptoms, 43 nurses, or about 54 percent, felt their symptoms improved while wearing a surgical or N95 mask, said Dr. Amiel Dror, a physician-scientist at Galilee Medical Center and Bar-Ilan University Azrieli Faculty of Medicine and the lead author on the study.Mask use was also more effective for the nurses with seasonal allergies than those with year-round symptoms. Wearing a mask did not solve the problem of itchy eyes, according to the September report, published in The Journal of Allergy and Clinical Immunology.Although the findings suggest that wearing a mask can reduce allergy symptoms for some people, the researchers noted that more study is needed. It could be that the nurses experienced fewer symptoms because, when they weren’t working, they were staying home and avoiding crowds during lockdowns, and thus had less exposure to allergens in the environment. But the fact that mask wearing, which covers the nose and mouth, was associated with improvements in nasal symptoms, but not eye irritation, suggests that masking probably did help reduce many allergy symptoms.In addition to filtering out allergens, wearing a mask also makes the air in our nasal cavities warmer and more humid, said Dr. Dror. “We know that dry air and cold air sometimes has the ability to elicit a reaction in the nose,” he said. “This is an extra benefit of wearing a mask. With all the bad, you can find some good.”Protection varies mask to mask, depending on the fit and, for cloth masks, the weave of the fabric. And unless you wear a mask at all times, you may still be affected by indoor allergens such as dust mites or pollen carried through open windows on spring breezes.“It can help, but it’s not necessarily going to take away all your symptoms,” said Dr. Sandra Lin, a professor of Otolaryngology — Head and Neck Surgery at Johns Hopkins School of Medicine. “Pretty much everyone’s wearing masks most of the time now, and people are still getting allergy symptoms.”Here are some more tips to reduce your symptoms during allergy season.Protect your eyes. Dr. Lang recommends people who suffer from allergies wear glasses or sunglasses when they’re outside, which helps block allergens like tree pollen from making direct contact with eyes.Wash and change your mask frequently. “The last thing you want is allergen getting trapped in it,” Dr. Parikh said. She recommends patients change their clothes when they get home and shower before sleep, to ensure that pollen doesn’t stick to their skin, and wash reusable masks frequently. The Centers for Disease Control and Prevention recommends washing a cloth mask after each use.Find a mask that doesn’t irritate your skin. Choosing the right mask for an allergy-prone wearer can also be important. People with sensitive skin may react to dyes in some fabric masks and should use perfume-free detergents. Or choose a surgical or medical grade mask, which are less likely to irritate skin. “My allergy sufferers have very sensitive skin because the same critters that make them sneeze or cough also can irritate their skin,” Dr. Parikh said.Talk to a doctor if your allergy symptoms are severe. “If people are continuing to have symptoms that interfere with normal activity — if they’re missing work, missing school, their sleep is disrupted at night — see a physician,” Dr. Lang said. “There are other ways we can help. You shouldn’t be suffering needlessly.”

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She Suffered Balance Issues for Years. Was It a Brain Tumor?

A visit to the dentist unexpectedly led to a resolution.The dental hygienist greeted her longtime patient enthusiastically. Unexpectedly, the 68-year-old woman burst into tears. “I feel so bad,” she said, her voice cracking with emotion. “I’m worried I might be dying.” She was always tired, as if all her energy had been sucked out. And she felt a strange dread that something awful was happening to her. And if that weren’t enough, for the past couple of weeks she had lost much of her hearing in her right ear. She was sure she had a brain tumor — though none of her doctors thought so. After offering sympathy, the dental assistant realized she had something more to offer: “We have a dental CT scanner. Should we get a CT of your head?” The patient was amazed. Yes — she would very much like a CT scan of her head. It would cost her $150, the technician told her. At that point, it seemed like a bargain. And, just like that, it was done. And there was a mass. It wasn’t on the right side, where she thought her trouble lay. It was on the left. And it wasn’t in her ear, but in the sinus behind her cheek. That was confusing. She thanked the tech for the scan. She had an ENT and would send the images to him to see what he thought. A History of Ear IssuesThat right ear had been giving the patient trouble for more than 20 years, she reminded her ear, nose and throat doctor in Prescott, Ariz., when she spoke with him. In her 40s she developed terrible vertigo. She was living in Atlanta then and saw an ENT there who told her she probably had Ménière’s disease, a disorder induced by increased pressure in the inner ear. The cause is unknown, though in some cases it appears to run in families. And it’s characterized by intermittent episodes of vertigo usually accompanied by a sensation of fullness in the ear, as well as tinnitus and hearing loss. These symptoms can be present from the start, but often develop over time. There’s no definitive test for the disease, though evidence of the increased pressure is sometimes visible on an M.R.I. Medications like antihistamines and steroids can mitigate the symptoms, but there is no treatment for the disease itself. The patient was encouraged when her vertigo went away after a few months, and she tried to forget about it, but her body wouldn’t let her. Two years later she developed a problem with her balance. It wasn’t the sense of motion she had felt with the vertigo. Instead, there were times when the simple action of walking seemed strangely unnatural; times when she found it difficult to walk in a straight line. It could last for weeks, then disappear for months. And she couldn’t predict its coming or going. It got so bad that she started using a hiking stick whenever she walked farther than her front yard.She went to a neurologist, who ordered an M.R.I. of her brain. The images showed a little patch of something on the right side of her skull, near her inner ear. But both he and the radiologist thought it wasn’t significant. Besides, it was in the wrong place to be causing her symptoms. Instead, her doctor sent her to physical therapy to treat a disorder known as benign paroxysmal positional vertigo (B.P.P.V.), the most common cause of vertigo, usually triggered by head movements. The inner ear has fluid-filled tubes called semicircular canals. The sensation of the fluid moving in these canals tells your brain the position of your body in the world and helps you keep your balance. B.P.P.V. occurs when small pieces of bone (otoliths) are dislodged and roll around on the sensitive surface of the semicircular canals, sending confusing signals to the brain about the body’s position in the world.Physical therapy is normally effective in the treatment of B.P.P.V., though it didn’t do much for this patient. Throughout all this, even though all her doctors agreed that her right ear was the source of her intermittent loss of balance and vertigo, she never had a problem with the ear itself. She never had earaches. Her hearing was perfect. And then one day, it wasn’t. Photo illustration by Ina JangBuzzing That Would Not StopTwo years earlier, when she was 66, she was awakened one morning by a loud buzz. It took her a minute to locate the sound. It was coming from inside her right ear. It sounded like a fluorescent light on its last legs. Tinnitus is what her ENT at the time called it. It was, he told her, just one more thing she would have to put up with. Those were not words the patient wanted to hear. It was so loud that at times it was hard to hear what people were saying. The buzz — or, sometimes, a siren — was so intense it could wake her up from a dead sleep. Sometimes it would quiet down, but it never went away. Never.When her own doctors had nothing to offer, the woman looked elsewhere. She saw chiropractors, naturopaths and doctors specializing in alternative medicine. She was treated with antibiotics, antivirals and lots and lots of supplements. Nothing helped. Then, just weeks before she went to her dentist, she woke up and could hardly hear at all out of that ear. Everything was muffled, as if that ear was underwater. Her current ENT prescribed prednisone to reduce any inflammation.But when he saw the dental CT, he immediately ordered a conventional CT of her head. The dental scan was developed to give a three-dimensional image of the jaw and teeth, so it can’t be expected to show the entire skull. The full CT confirmed that there was a small mass in the left sinus. Based on its appearance, her doctor suspected it was a remnant of an infection from years before. But on the right side there was something else: A mass about the size of a strawberry had destroyed much of the mastoid bone just behind her ear. It was in the same place as the much smaller abnormality seen in the first M.R.I. years earlier. Now it was large enough to compress one of the vessels leading to the jugular vein. The radiologist said it looked like an infection. Or possibly a rare kind of bone cancer. Stray Cells in the BrainWith cancer a possibility, the patient decided she needed a second opinion. She reached out to the Arizona branch of the Mayo Clinic, in Phoenix, and was scheduled to see Dr. Peter Weisskopf two weeks later. Weisskopf listened as the patient described the vertigo, tinnitus and loss of hearing, along with the debilitating fatigue and terrifying sense of impending doom. “I’m not sure this mass could cause all that,” he told her, but he agreed that an M.R.I. would provide important diagnostic information. He suspected that she had something known as a cholesteatoma. These are benign growths of cells that get trapped inside the ear — or, rarely, as in this patient’s case, inside the brain — and start to grow. Sometimes these cells are imported into the ear after a chronic infection, but most of the time they get left there during fetal development. Weisskopf reviewed the M.R.I. The brain tissue showed up, as expected, as stripes of light and dark gray surrounded by fluid, which appears black. But just behind this patient’s ear, nestled into the lower edge of the mastoid bone of the skull, was a big bright cloud of white. Based on that appearance, Weisskopf knew what she had. It was a cholesteatoma. Although this is not a cancer, these sorts of tumors have to be removed. Left in place, they continue to enlarge until they cause real trouble. The patient was eager to have the thing removed. She felt certain that it had to be behind the symptoms she had been living with these past few years. Removing the large mass took two operations, the second one late last spring. But it was worth it, the patient told me. The worst symptoms are completely gone. Her fatigue and sense of oppression and doom disappeared after the first surgery. But even after the second, she still has the tinnitus, which is very loud at times. She still has trouble with her balance. Her hearing is not as good as it used to be. Weisskopf doesn’t believe the mass caused the patient’s symptoms. The patient respectfully disagrees; where it really mattered, with her mood, her sense of well-being, she feels back to something like her old self. And even though her doctor can’t see the link, she’s certain it all came from that growth, which, she thinks, maybe wasn’t quite as benign as her doctors and the textbooks say.Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share with Dr. Sanders, write her at Lisa .Sandersmd@gmail.com.

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Covid: Australia falls 85% short of vaccine delivery goal

SharecloseShare pageCopy linkAbout sharingimage copyrightEPAAustralia has fallen 3.4 million doses short of its target of delivering four million Covid vaccinations by 31 March, prompting criticism of the government.The 85% shortfall comes two days after Brisbane entered another snap lockdown to combat a small outbreak.Last week the government said the vaccine rollout did not demand urgency given Australia’s low infection rates.The country has recorded 909 deaths and 29,300 cases since the pandemic began – far fewer than many other nations.But sporadic outbreaks have led to six lockdowns in cities in recent months. Critics say situations like Brisbane’s outbreak show why a quick vaccine programme is still needed.Brisbane’s two clusters have been linked to a nurse and a doctor who contracted the virus from a Covid ward at the same hospital. It’s unclear why those health workers had not yet been vaccinated, officials said.Australian PM is vaccinated as rollout beginsQantas says vaccines will be required to fly Australia to send Papua New Guinea vaccinesCritics have accused the government of mishandling the rollout, which began on 22 February – later than in many countries.Australia is administering the Pfizer and AstraZeneca vaccines and has a rate of 2.3 vaccines per 100 people. That is expected to increase in coming months as vaccine access is opened up to the wider population.On Wednesday, Health Minister Greg Hunt said a record 72,826 vaccinations had been given in the past day – taking the total to 670,000.”That’s showing that the national vaccination programme is accelerating exactly as intended in the manner that was intended,” he told reporters.But in January, Prime Minister Scott Morrison promised to have four million people inoculated with their first shot by March.Earlier this month, the government pushed that target back to April, and said six million people would be vaccinated by mid-May. It has also dialled back a promise to have every Australian fully vaccinated by October – now saying that everyone will have received a first shot by then.Slowed rolloutAustralia is currently up to stage two of its four-phase rollout for its 25 million population.Doses are being offered to people over 70, those in aged care homes, frontline health workers, emergency services workers, Aboriginal and Torres Strait Islander people over 55, and people with underlying health conditions.Authorities have not specified why the pace has been so slow, but issues such as booking technicalities have been reported. There are also reports that some people are choosing to not get the vaccine.Natural disasters – such as the massive floods in eastern Australia last week – have also disrupted the rollout.Earlier this month, the EU blocked a shipment of AstraZeneca doses to Australia, arguing there was a greater need for them in Europe.Australia said the one shipment of 250,000 doses would not greatly affect its own programme, as it built up its own manufacturing capability. However, Australia has asked the EU to review the ban on its order, which Mr Morrison said had been paid for.Labor opposition leader Anthony Albanese said the government, by its own admission, could not blame international supply issues.”They said that target wasn’t dependant on anything else and they would certainly reach the target,” he told the ABC. “Yet again it’s an example of how Scott Morrison is always strong on announcement and weak on delivery.”Concerns in BrisbaneQueensland’s capital reported two more community transmission cases on Wednesday, bringing the outbreak to 15 infections in total.There are fears that the city’s three-day lockdown, due to finish on Thursday, will need to be extended. Contact tracers are scrambling to track down infected people and have so far placed more than 1,000 of their close contacts in quarantine.The lockdown has forced many in Queensland and interstate to cancel their Easter and school holiday plans. Queensland’s state economy is heavily reliant on tourism – and operators have forecast that the three-day lockdown has caused a A$35m (£19m; $26m) loss.

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